Hympavzi lowers bleeding rates for hemophilia patients with inhibitors
Preventive treatment found effective in Phase 3 trial: Top-line data
Preventive treatment with Hympavzi (marstacimab-hncq) can effectively reduce bleeding rates in people with hemophilia A or B who have inhibitors, or antibodies against standard replacement therapies, according to top-line data from a Phase 3 clinical trial.
Hympavzi’s developer Pfizer said it’s now planning to discuss these data with regulatory authorities in hopes of getting the prophylactic (preventive) therapy approved for hemophilia patients who have inhibitors. The company did not provide a timeframe for when applications are expected.
“These encouraging results demonstrate Hympavzi’s potential to help people living with hemophilia A or B with inhibitors,” Michael Vincent, MD, PhD, chief inflammation and immunology officer at Pfizer, said in a company press release, which characterized the trial data as “positive,” and said the therapy “demonstrates superiority.”
According to Pfizer, Hympavzi was given in the Phase 3 BASIS trial (NCT03938792) via “a straightforward, once-weekly subcutaneous [under-the-skin] injection that required minimal preparation.”
Hemophilia overall is characterized by a deficiency in proteins that are needed for the blood to clot — specifically, factor VIII, or FVIII, in the case of hemophilia A and factor IX, or FIX, in hemophilia B. Standard treatment for both of these types of hemophilia involves replacement therapy, in which a version of the missing clotting factor is administered as medication to treat or prevent bleeds.
Frequent complications seen for hemophila patients with inhibitors
Some people with hemophilia will develop neutralizing antibodies against standard replacement therapies. These antibodies are called inhibitors because they can stop replacement therapies from working as well as they should.
Davide Matino, MD, the principal investigator of the BASIS trial, noted that “patients with inhibitors tend to face frequent complications.”
As such, “navigating the treatment landscape can introduce complexities and increase disease burden,” said Matino, also an associate professor of medicine at McMaster University in Canada.
Hympavzi is an antibody-based therapy that’s designed to promote blood clotting by blocking the activity of tissue factor pathway inhibitor (TFPI), a protein that normally acts to prevent unneeded clotting. By inhibiting TFPI, Hympavzi is expected to promote blood clotting through a mechanism that bypasses the need for FVIII or FIX.
The goal of the treatment is thus to help prevent bleeds in people with either type of hemophilia, irrespective of inhibitor status.
Administered weekly by subcutaneous injection, Hympavzi is currently approved in the U.S. and the European Union as a prophylactic treatment for people, ages 12 and older, with hemophilia A or B who do not have inhibitors.
Reduction in bleeding rates of over 90% seen with Hympavzi in trial
The BASIS trial tested Hympavzi in nearly 200 male patients, ages 12 to 74, with hemophilia A or B. The study included individuals with or without inhibitors.
Findings from patients without inhibitors formed the basis for the therapy’s approval in that population. In those patients, preventive treatment with Hympavzi led to significant reductions in annualized bleed rates compared with on-demand and prophylactic treatment with standard replacement therapy.
The new data cover 48 participants who were positive for inhibitors. These patients first underwent a six-month observational period in which they only received standard on-demand therapy with bypassing agents to manage any bleeds that occurred. Then, all received prophylactic treatment with Hympavzi for one year.
The results showed that, during the observational period, these individuals were experiencing nearly 20 bleeds per year that required treatment. By contrast, while on prophylactic treatment with Hympavzi, the annualized bleeding rate for treated bleeds was less than two bleeds per year — corresponding to a 93% reduction.
The strong bleed reduction with Hympavzi compared to on-demand treatment in the Phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options.
Hympavzi also was found to be superior to standard on-demand treatment in its ability to lower the rates of spontaneous, joint, and total bleeds.
“The strong bleed reduction with Hympavzi compared to on-demand treatment in the Phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options,” Matino said.
Safety data from those who were inhibitor-positive were generally consistent with findings seen in patients who don’t have inhibitors, according to Pfizer. No deaths or abnormal clotting problems were reported.
Vincent said these new data show Hympavzi is “a generally well-tolerated treatment option that could offer bleed protection with … once-weekly subcutaneous administration in a pre-filled pen for patients with inhibitors, if approved in this patient population.”
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